P346: THE ROLE OF CYTOKINES, TNF, TGFΒ1 AND NEUTROPHIL-TO-LYMPHOCYTE RATIO IN THE COURSE OF THE ACUTE LEUKEMIA
Authors: V. Barilka, V. Matlan, S. Prymak, O. Shalay
Journal: HemaSphere (2022)

Background: Lymphocytes (Lym) and mature segmental neutrophils (Neu) together with blasts are most commonly detected in the peripheral blood (PC) of patients (pta) with acute leukemia (AL). Besides, Neu, Lym and blast cells are an important source of transforming growth factor β1 (TGFβ1), tumor necrosis factor (TNF) production. Accumulation of TNF, TGFβ1 in the plasma of AL pts is considered an unfavorable sign in AL. However, the role of TNF, TGF β1 in the relationship with neutrophil-to-lymphocyte ratio (NLR) in the course of AL is not definitively established. Aims: Determine the role of cytokines, TNF, TGF β1 in the relationship with NLR to assess the course of AL. Methods: 42 adult AL pts were examined before treatment, who at the time of the examination had blast cells in the peripheral blood (52.54 ± 5.63 x 109 / L). The NLR was calculated from peripheral blood cell counts obtained at the time of diagnosis of AL by dividing the Neu count by the Lym count. The median NLR (0.99) was used to dichotomize patients into high- NLR and low- NLR groups. The concentration of TNF, TGF β1 was determined by biological methods using sensitive cell lines L929 and CCL 64, respectively. Statistical processing of the results was estimated by the value of p ˂ 0, 005. The correlation between the indicators was estimated by the value of r. Results: There were 25 people in the low-NLR group. Median age 66 years (36 - 81 years). Among the pts were 9 people with ALL and 16 people with AML. Number of blasts 55, 83 ± 6.38 x 109 / L; New count was 11.73 ± 2.95 109 / L, Lym count - 21.27 ± 3.64 109 / L. The NLR index is 0.53 ± 0.09. In this group, 88% of pts died in the short term without achieving remission, the remaining 12% of pts had short-term remission. The concentration of TNF in plasma was 1.20 ± 0.13 ng / ml, TGF β1 - 4.02 ± 0.48 ng / ml, which in both cases was higher than in healthy individuals (p˂0.001 and p˂0.05, respectively). TNF levels were positively correlated with Lym (r = 0.30) and blasts (r = 0.40), suggesting a possible role for TNF in neoplastic clone survival. There were 17 people in the high-NLR group, including 10 pts with ALL and 7 people with AML who achieved remission. The median age is 38 years (from 16 to 68 years). The number of blasts was 33.20 ± 9.67 x 109 / L and was significantly lower than in the low-NLR group (p˂0.05); New count was 22.23 ± 0.10 x 109 / L; Lym count - 22.83 ± 3.04 109 / L. The NLR was 1.24 ± 0.16. In this group, 94% of pts had remission. Plasma TNF and TGF concentrations were lower than in the low-NLR group, apparently due to lower blast content. However, no statistical difference in cytokine concentration between the compared groups was found. Summary/Conclusion: More favorable prognostic features in AL could be NLR, the median of which is equal to or greater than 0.99. Under these conditions, a decrease in the number of blast cells, the concentration of cytokines TNF and TGF β1 in the plasma and the achievement of remission were observed. The data obtained may indicate a prognostic role of Neu and Lym blood subpopulations in the course of AL and in the relationship with cytokines, TNF and TGF β1, may be potential targets for the correction of treatment of AL pts.